Neuroplasticity in Alzheimer's disease

Abstract

Ramon y Cajal proclaimed in 1928 that “once development was ended, the founts of growth and regeneration of the axons and dendrites dried up irrevocably. In the adult centers the nerve paths are something fixed, ended and immutable. Everything must die, nothing may be regenerated. It is for the science of the future to change, if possible, this harsh decree.” (Ramon y Cajal, 1928). In large part, despite the extensive knowledge gained since then, the latter directive has not yet been achieved by ‘modern’ science. Although we know now that Ramon y Cajal's observation on CNS plasticity is largely true (for lower brain and primary cortical structures), there are mechanisms for recovery from CNS injury. These mechanisms, however, may contribute to the vulnerability to neurodegenerative disease. They may also be exploited therapeutically to help alleviate the suffering from neurodegenerative conditions. Published 2002 Wiley‐Liss, Inc.

Alzheimer disease and neuroplasticity: New approaches and new targets in pharmacotherapy

“…Memory loss in AD may result from synaptic dysfunction that precedes large scale neurodegeneration, where the synapseto-neuron ratio is decreased about 50% (15,(60)(61)(62). There is prominent neuronal loss in AD, especially in hippocampal area and enthorinal and association cortex (15,63,64), which disrupts memory-related circuitry in the brain, as mentioned above. Neuronal loss in these formations results in synapse loss due to deafferentation of target regions.…”

“…Presently, concerning the pathological mechanism, the neuroplasticity hypothesis of CNS disorders including AD are again gaining importance (14,15). Directly focusing on the causes of the damage of synaptic elements, and development of new therapeutic approaches devoted to reverse the impaired neuroplasticity induced by the disorder may be a more effective strategy, and provide more consistent solutions in the treatment of AD.…”

“…PS1 is necessary for normal neurogenezis and survival, and localizes to synaptic membranes and neurite growth cones. Presenilins are related to intracellular trafficking, developmental signaling pathways and Ca 2+ homeostasis (15,(37)(38)(39).…”

“…The various structural elements that embody plasticity include LTP, synaptic efficacy, synaptic remodeling, synaptogenesis, neurite extension including axonal sprouting and dentritic remodeling, and neurogenesis and recruitment. In a more comprehensive logic, phenomenological processes that are apparent in plasticity are: synapses (electrical, biochemical, structural), neurite (axon, dendrite), neuron cell bodies, anterograde (toward distal neurites) and retrograde (from distal neurites) transport, cell interactions, neuronal networks or pathways, and behavioural, psychological and sociological activities (15). Unfavorable neuroplasticity is characterized by an adverse adaptation of the brain and appears in a number of CNS disorders.…”

Stroke occurring in patients with cognitive impairment or dementia

“…However other studies have shown that this effect is modest and should not prevent the administration of rt-PA 46 . Theoretically, patients with pre-stroke cognitive impairment may have a higher sensitivity to the toxic effect of rt-PA and a lower capacity to recover from brain injury 47 . Despite these theoretical reasons for the reduced efficacy of rt-PA and worse safety profiles, no study has found an increased rate of haemorrhagic transformation after intravenous rt-PA in patients with pre-stroke cognitive impairment 19,20,48,49,50 .…”